Novel Retinal Lesion in Ebola
Survivors, Sierra Leone, 2016
Paul J. Steptoe, Janet T. Scott, Julia M. Baxter, Craig K. Parkes, Rahul Dwivedi,
Gabriela Czanner, Matthew J. Vandy, Fayiah Momorie, Alimamy D. Fornah, Patrick Komba,
Jade Richards, Foday Sahr, Nicholas A.V. Beare, Malcolm G. Semple
We conducted a case–control study in Freetown, Sierra
Leone, to investigate ocular signs in Ebola virus disease
(EVD) survivors. A total of 82 EVD survivors with ocular
symptoms and 105 controls from asymptomatic civilian and
military personnel and symptomatic eye clinic attendees un-
derwent ophthalmic examination, including widefield retinal
imaging. Snellen visual acuity was <6/7.5 in 75.6% (97.5%
CI 63%–85.7%) of EVD survivors and 75.5% (97.5% CI
59.1%–87.9%) of controls. Unilateral white cataracts were
present in 7.4% (97.5% CI 2.4%–16.7%) of EVD survivors
and no controls. Aqueous humor from 2 EVD survivors with
cataract but no anterior chamber inflammation were PCR-
negative for Zaire Ebola virus, permitting cataract surgery.
A novel retinal lesion following the anatomic distribution of
the optic nerve axons occurred in 14.6% (97.5% CI 7.1%–
25.6%) of EVD survivors and no controls, suggesting neu-
ronal transmission as a route of ocular entry.
T he most recent Ebola virus disease (EVD) outbreak
in West Africa is the largest outbreak in history. As
of March 27, 2016, an estimated 3,956 persons in Sierra
Leone had died from EVD, and 10,168 had survived (1).
The scale of this epidemic has enabled the study of large
numbers of survivors, facilitating the characterization of
post-Ebola syndrome. Ocular symptoms have been report-
ed, with incidence among survivors ranging from 14% to
60% (2–4). Evidence of acute uveitis on ophthalmic ex-
amination ranges from 18% to 58% (4–7). Classification of
uveitis also varies and has been reported as 36%–62% ante-
rior, 3% intermediate, 26%–36% posterior, and 18%–25%
panuveitis (4,8). However, little is known regarding the
Author affiliations: University of Liverpool, Liverpool, UK
(P.J. Steptoe, J.T. Scott, G. Czanner, N.A.V. Beare, M.G. Semple);
Royal Liverpool Hospital, Liverpool (P.J. Steptoe, J.M. Baxter,
C.K. Parkes, R. Dwivedi, N.A.V. Beare); National Institute for
Health Research Health Protection Research Unit in Emerging
and Zoonotic Infections, Liverpool (J.T. Scott, M.G. Semple);
Connaught Hospital, Freetown, Sierra Leone (M.J. Vandy); 34th
Military Hospital, Freetown (F. Momorie, A.D. Fornah, P. Komba,
F. Sahr); Public Health England Laboratory, Makeni, Sierra Leone
(J. Richards)
DOI: https://dx.doi.org/10.3201/eid2307.161608
1102 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 23, No. 7, July 2017
medium- to long-term visual outcome of survivors or the
rates of background uveitis and chorioretinal lesions within
the local population.
Two published cases (9–11) and 2 case series (7,12)
included fundus imaging, which attribute a range of retinal
lesions to Ebola uveitis. Fourteen weeks after EVD dis-
charge, a unilateral anterior hypertensive uveitis developed
in 1 survivor and soon progressed into an aggressive anteri-
or scleritis and intermediate uveitis. Viable Zaire Ebola vi-
rus (EBOV) was detected from the aqueous humor 9 weeks
after the clearance of viremia (9). The duration of EBOV
ocular persistence remains unknown, although repeated
aqueous humor testing in the same survivor was negative
for EBOV by quantitative reverse transcription PCR (qRT-
PCR) 1 year later (10). Recurrences up to 13 months after
EVD discharge have been reported, but confirmation of
Ebola etiology through aqueous humor analysis was not
conducted (7). Because of the unknown prevalence and
duration of EBOV persistence in aqueous humor, survi-
vors’ access to cataract surgery is still restricted. Our study
aimed to detect if any specific retinal signs can be attributed
to past EVD in survivors, to describe the implications for
visual acuity, and to assess for EBOV persistence in survi-
vors with cataracts amenable to cataract surgery where no
intraocular inflammation was present.
Methods
Study Design
We conducted a case–control prospective study comparing
ophthalmic findings between EVD survivors and a control
group during January–June 2016. Reporting of the findings
is in accordance with guidelines set forth in the Strengthen-
ing the Reporting of Observational Studies in Epidemiol-
ogy (STROBE) statement (13).
Study Population
We searched a database of EVD survivors from the 2014–
2016 EVD epidemic who had attended the EVD survivors
clinic at 34th Regiment Military Hospital in Freetown, Si-
erra Leone, for patients who had reported ophthalmic com-
plaints at any of their follow-up appointments (2). Patients

were contacted by telephone and invited to attend the oph-
thalmology clinic for review. EVD survivors from other
medical facilities in the region who had reported ophthal-
mic complaints also attended the clinic through word of
mouth and electronic social media networking from other
survivors. EVD survivor status was verified by the posses-
sion of a valid discharge certificate from an Ebola treatment
center. Date of acute admission, date of discharge, and lo-
cation of the Ebola treatment center were recorded from
each discharge certificate.
Controls were recruited from ophthalmically symp-
tomatic and asymptomatic local military personnel, their lo-
cal family members, and symptomatic civilians. Survivors
and controls were invited to participate in English or Krio,
as preferred, with local ophthalmic nurses acting as inter-
preters. Consent was confirmed by fingerprint or signature.
Ocular Examination
Data were collected on first visit. The onset and nature of
ocular complaint, and any systemic complaints were re-
corded on a standardized form before examination. Patients
underwent visual acuity testing with either Snellen or Il-
literate E-chart acuity methods. Snellen visual acuity was
grouped into visual acuity ranges according to the Interna-
tional Classification of Diseases, Ninth Revision, Clinical
Modification, and reported as patient’s best eye vision.
Ocular anterior chamber assessment was conducted
with a table-mounted slit lamp by 3 local ophthalmic clini-
cal officers. The initial 35% of anterior chamber examina-
tions were supervised and verified by an ophthalmologist
from the United Kingdom. Patient examinations thereaf-
ter were conducted by local clinical officers alone with a
telecommunication link for advice if required. Assessment
of anterior chamber inflammation was graded according to
the Standardization of Uveitis Nomenclature criteria (14).
Intraocular pressures were measured by automated pneu-
matic tonometry (Canon TX-F; Melville, NY, USA); if
out of reference range, this measure was repeated by using
Goldmann applanation tonometry.
Widefield retinal images were obtained from patients
with the use of a nonmydriatic Daytona Scanning Laser
Ophthalmoscope (fundus camera; Optos, Dunfermline,
UK). Optical coherence tomography was undertaken
with the use of a Topcon DRI Triton swept source opti-
cal coherence tomography (Topcon Corporation, Tokyo,
Japan). Posterior subcapsular and cortical cataract were
graded from a comparison of standard images used in the
Lens Opacities Classification System III (15) and applied
to acquired fundus images. White cataracts were identified
during patient examination, and fundus imaging was not
possible. Presence of signs in the vitreous indicative of in-
termediate uveitis were also recorded from scanning laser
ophthalmoscope imaging.
Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 23, No. 7, July 2017
Retinal Lesion in Ebola Survivors, Sierra Leone
All clinical and artifactual signs present on scanning
laser ophthalmoscopic imaging and corresponding auto-
fluorescent imaging were recorded, grouped, and incor-
porated into an original classification form with associ-
ated standard images and descriptions (online Technical
Appendix 1, https://wwwnc.cdc.gov/EID/article/23/7/16-
1608-Techapp1.pdf). All images were graded for these fea-
tures by 2 independent, masked ophthalmologists from the
United Kingdom with specialist interests in medical retina.
Certainty of positive findings were quantified as “yes, defi-
nitely,” defined as >90% certainty, or “yes, questionably,”
defined as >50% certainty. Mutual agreements of definite
or probable certainty were counted. Where discordance ex-
isted between findings, a third independent consultant oph-
thalmologist made final arbitration.
Paracentesis of the anterior chamber was performed at
a slit lamp with a sterile 30-gauge needle while the clini-
cian was wearing personal protective equipment. After in-
formed consent was obtained, the procedure was conducted
on 2 patients with white cataracts but no clinical signs of
anterior chamber inflammation. At the time of sampling,
the 2 survivors were 430 and 482 days postdischarge from
their respective Ebola treatment centers. By using an an-
terior chamber tap procedure protocol (online Technical
Appendix 2, https://wwwnc.cdc.gov/EID/article/23/7/16-
1608-Techapp2.pdf), 0.1 mL of aqueous humor was ob-
tained in both cases. Both specimens were delivered to the
Public Health England laboratory (Makeni, Sierra Leone)
for analysis for EBOV RNA on qRT-PCR assay. Testing
was performed with the use of the standard institutional op-
erating protocols by clinical laboratory technologists who
were trained in the safe handling of infectious pathogens.
Statistical Methods
We reported results per patient and grouped by subject by
using IBM SPSS version 22 (http://www-01.ibm.com/sup-
port/docview.wss?uid=swg27038407). Where data were
missing, we reduced the denominator for each variable. We
double-checked 10% of data entry and found 0% transcrip-
tion errors. We calculated 97.5% CIs by using the exact
binomial (Clopper-Pearson) method (16); no overlap be-
tween CIs indicates a statistically significant result. Fisher
exact statistical value was calculated for significant results.
The study was approved by the Sierra Leone Ethics
and Scientific Review Committee on January 29, 2016. In
addition, the study was authorized by the Pharmacy Board
of Sierra Leone.
Results
The numbers of patients recruited and examined at 34th
Regiment Military Hospital were 82 EVD survivors (161
eyes; 2 missing retina images and 1 prosthetic eye) and 105
never-infected controls (208 eyes; 2 missing retinal images).
1103
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Male-to-female ratio was 1:1.48 of EVD survivors and
1:0.64 of controls. Median age at time of ophthalmic exami-
nation was 28 years (interquartile range [IQR] 22–38 years)
for EVD survivors and 41 years (IQR 30–48 years) for con-
trols. Median time from Ebola treatment unit discharge to
ophthalmic examination for survivors was 411 days (n =
70) (IQR 368–470 days). Ophthalmic examination findings
were summarized for survivors and controls (Table).
We subclassified pigmented and nonpigmented retinal
lesions into 10 discrete groups (online Technical Appendix
1) and noted frequency of each lesion type (Figure 1). We
found no occurrences of the retinal lesion documented in a
previous case report (9) in this EVD survivor cohort. Only
the type 6 subcategory of retinal lesion was observed exclu-
sively in EVD survivors, occurring in 12/82 (14.6% [97.5%
CI 7.1%–25.6%]) EVD survivors and 0/105 controls (0%

Table. Ophthalmic examination findings in a case–control study of ocular signs in Ebola virus disease survivors, Sierra Leone, 2016*
Survivors Controls
Finding No. % (97.5% CI)† No. % (97.5% CI)†
Best eye visual acuity‡
Missing data 3 – 56 –
Normal 59 74.7 (62.1–84.9) 37 75.5 (59.1–87.9)
Near normal 18 22.8 (13.1–35.1) 8 16.3 (6.4–31.6)
Moderate 1 1.3 (0–7.8) 3 6.1 (1–18.6)
Severe 1 1.3 (0–7.8) 0 0 (0–8.6)
Profound 0 0 (0–5.5) 1 2 (0–12.3)
Near total 0 0 (0–5.5) 0 0 (0–8.6)
Total 0 0 (0–5.5) 0 0 (0–8.6)
Intraocular pressure, mmHg
Missing data 35 – 74 –
Hypotonous (<5) 5 10.6 (3–25) 0 0 (0–13.2)
Reduced (6–10) 5 10.6 (3–25) 3 9.7 (1.6–28.2)
Within normal range (11–21) 35 74.5 (57.6–87.3) 26 83.9 (63.8–95.4)
Elevated (22–29) 1 2.1 (0–12.8) 2 6.5 (0.5–23.7)
High (>30) 1 2.1 (0–12.8) 0 0 (0–13.2)
Worst eye cup:disc ratio§
Bilateral ungradable 1 – 0 –
Unilateral ungradable 11 – 8 –
Normal (0.1–0.6) 73 90 (80.1–96.2) 79 75.2 (64.5–84.1)
Moderate (0.7–0.8) 7 8.6 (3.1–18.3) 23 21.9 (13.5–32.3)
Advanced (>0.9) 1 1.2 (0–7.6) 3 2.9 (0.5–9)
Cataract
All cataract 19 23.2 (13.6–35.3) 18 17 (9.7–27)
White cataract 6 7.3 (2.3–16.5) 0 0 (0–4.1)
White cataract with hypotony, IOP <5 mm Hg¶ 4 80 (23.6–99.7) NA NA
Active anterior uveitis
Missing data 13 – 67 –
Anterior chamber cells present 5 7.3 (2–17.4) 4 10.5 (2.4–27)
Previous anterior uveitis
Missing data 12 – 65 –
Signs of previous anterior uveitis# 7 10 (3.6–21) 0 0 (0–10.4)
Vitreous signs**
Signs suggestive of active or past intermediate uveitis 8 (9.8) 9.8 (3.8–19.6) 14 13.3 (6.9–22.5)
Retinal signs**
Retinal hemorrhages 0 0 (0–5.2) 2 1.9 (0.2–7.5)
Retinal neovascularization 0 0 (0–5.2) 1 1 (0–5.9)
Papilledema 0 0 (0–5.2) 0 0 (0–4.1)
Retinal vasculitis 0 0 (0–5.2) 4 3.8 (0.8–10.4)
Macula hole 0 0 (0–5.2) 1 1 (0–5.9)
Retinal tears 1 1.2 (0–7.5) 1 1 (0–5.9)
Retinal detachment 0 0 (0–5.2) 2 1.9 (0.2–7.5)
Asteriod hyalosis 0 0 (0–5.2) 1 1 (0–5.9)
Myelinated nerve fibers 0 0 (0–5.2) 1 1 (0–5.9)
Benign flecked retina 1 1.2 (0–7.5) 0 0 (0–4.1)
Geographic retinal darkening and variants 16 19.5 (10.7–31.2) 13 12.4 (6.2–21.4)
White without pressure 18 22 (12.6–34) 20 19 (11.2–29.2)
*IOP, intraocular pressure; NA, not available; –, not applicable.
†Calculated by using exact binomial Clopper-Pearson method.
‡Grading based on International Classification of Diseases, Ninth Revision, Clinical Modification (true Snellen fractions).
§When only 1 cup:disc ratio was gradable, only that ratio was used for analysis.
¶Missing data on 2 patients.
#Posterior synechiae and/or pigment on anterior lens capsule, keratic precipitates but no anterior chamber inflammation, or both.
**Graded based on widefield retinal image.

1104 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 23, No. 7, July 2017
 Retinal Lesion in Ebola Survivors, Sierra Leone

Figure 1. Prevalence of retinal scar lesion types in a case–control study of ocular signs in Ebola virus disease survivors, Sierra Leone,
2016. Type 1, uniform pigmented lesion; type 2, uniform pigmented lesion with gray halo; type 3, uniform pigmented lesion with lacunae;
type 4, pigmented lesion with deep surrounding atrophy; type 5, previously described lesion attributed to Ebola (8); type 6, angulated
lesions (peripapillary and/or peripheral); type 7, indistinct small pigmented lesions; type 8, irregularly pigmented vascular projection
lesion; type 9, pigmented curvilinear peripheral bands; type 10, optic disc projection to macula lesion. Error bars indicate 97.5% CI.
Asterisk indicates statistical significance (p<0.01) based on Fisher exact statistic value (2.7 × 105).

[97.5% CI 0%–4.1%]) (p<0.01). In 50% of EVD survivors,
this type of lesion was observed bilaterally.
Two fundal distributions of type 6 lesions were evi-
dent: isolated or multifocal lesions in the peripheral retina
or peripapillary lesions observed emanating from the optic
disc (Figure 2). Each lesion shape was variable but often
exhibited characteristic sharp angulations, resembling a
diamond or wedge (Figure 3). Surrounding these lesions
was a well-demarcated area of darkened retina in compar-
ison with the adjacent retina. Presence of any retinal le-
sions of types 1–10, excluding type 6, were observed in
21/82 (25.6% [97.5% CI 15.5%–38%]) EVD survivors and
25/105 (23.8% [97.5% CI 15.1%–34.4%]) controls.
The aqueous humor of 2 EVD survivors with white
cataract and no anterior chamber inflammation was nega-
tive for EBOV RNA on qRT-PCR assay. Postprocedure
conjunctival swabs also were negative. The aqueous humor
sampling procedure was uncomplicated and well-tolerated.
No complications were reported on follow up.
Discussion
This case–control study identified a novel retinal sign that
appears to be specific to EVD survivors. This sign occurred
among a local population with a high rate of background
chorioretinal disease. Uveitis after EVD has been reported
(3,8), and a recent case report included a published fundus
image from a survivor with a chorioretinal lesion attributed
to EVD (9). That patient went on to have panuveitis.
The retinal lesions specific to EVD survivors were lo-
cated either adjacent to the optic disc or in the fundus periph-
ery. In the 8 cases in which lesions appear adjacent to the
optic disc, their curvilinear projections from the disc margin
appear to align with the anatomic pathways of the retinal
ganglion cell axons that constitute the optic nerve. This dis-
tribution suggests a neurotrophic spread into the eye from
the optic nerve and along the retinal ganglion cell axons.
The other possible mode of entry into the eye is hematolog-
ic. Although the retinal ganglion cell axons often have par-
allel curvatures around the retinal arcade vessels, the lesions
clearly follow the nerve fiber distribution in the absence of
major vessels (Figure 1, panels A and C). Furthermore, we
have not found any signs suggestive of associated vascular
involvement, such as vasculitis, vascular occlusions, retinal
ischemia, or secondary neovascularization, to support a he-
matologic spread. Neurotrophic properties are increasingly
being recognized in EBOV (18). West Nile virus disease,
caused by a known neurotropic virus, is associated with reti-
nal lesions that follow a similar pattern of distribution to the
pattern we have observed in our study (19).
Each Ebola lesion shape is variable, but a character-
istic angulated appearance often resembling a diamond or
wedge shape appears unique (Figure 2). As far as we are

Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 23, No. 7, July 2017 1105
RESEARCH

Figure 2. Composite scanning laser ophthalmoscope retinal images showing type 6 Ebola peripapillary and peripheral lesions, observed
following the anatomic distribution of the ganglion cell axons (retinal nerve fiber layer), in a case–control study of ocular signs in Ebola
virus disease survivors, Sierra Leone, 2016. A) Example 1, right eye. B) Illustration of the ganglion cell axon anatomic distribution.
Courtesy of W.L.M. Alward. C) Example 2, right eye. Asterisks indicate curvilinear lesions distinct from the retinal vasculature. White
arrowhead indicates retinal nerve fiber wedge defect.

aware, the appearance of these lesions is not characteristic
of any other retinal disease. The reason for the sharp angu-
lated appearance of these lesions might be explained by the
tight triangular packing of the retinal cone mosaic (Figure
3, panel D) (17,20). The regular pattern of the photorecep-
tor triangular mosaic is disrupted by larger blue cones (17)
and diminishes with eccentricity (20), which might explain
the variability in shape. Optical coherence tomography in-
dicates that these lesions are limited to the retina (Figure
3, panel B), and the resemblance of the lesion shape to the
photoreceptor mosaic suggests that the ganglion cell axons
act merely as a means of transportation to the photoreceptor
end target.
Despite the proximity of the lesions to the optic nerve
head, we observed no optic nerve head swelling or pallor in
our study. This fact is in contrast to the 10% of optic nerve
swelling reported in 1 abstract (5), although the time from
acute infection to ophthalmic examination in that case was
not stated. This difference might be attributable to varying
durations since acute infection, allowing for any potential
disc swelling to resolve in our cohort, for whom the me-
dian time since discharge was 411 days. Further optic nerve
functional assessment, such as visual field analysis or color
vision testing, has yet to be conducted.
The Ebola retinal lesions did not affect visual acu-
ity. Overall, no difference was observed in uncorrected
visual acuity between EVD survivors and controls. The
most common cause of visual impairment in EVD survi-
vors was white cataract (7.3%), which was accompanied
by hypotony (low intraocular pressure) in 80% of EVD
survivors. Hypotony suggests inadequate aqueous humor
production and can limit the visual potential of an eye
through complications such as retinal folds at the macula
(i.e., hypotensive maculopathy).
Concern exists about the safety of cataract surgery in
EVD survivors in Sierra Leone because of the unknown
duration of EBOV ocular persistence. A sample size of 2
negative aqueous humor samples in this study is too small
to make any definitive conclusions but shows that EBOV
does not necessarily persist in aqueous humor in those with
cataract but no ongoing intraocular inflammation. This find-
ing suggests that cataract surgery can be conducted safely,
providing an opportunity to restore vision and remove the
stigma of EVD survivor status associated with having a vis-
ible white cataract. At present, we would recommend that
anterior chamber sampling with EBOV PCR and a negative
result should precede cataract surgery. However, cataract
surgery might be challenging and visual outcomes disap-
pointing in cases of secondary hypotony, which occurred
in 80% of EVD survivors.
Before this study, only 1 aqueous humor sample had
been obtained in an EVD survivor (9), enabling the de-
tection of viable EBOV in aqueous humor during acute
uveitis 9 weeks after discharge from hospital (9). Virus
persistence in aqueous humor has also been observed
in uveitis after Marburg virus infection (21), becoming
negative on being repeated at 10 weeks (22). In EVD and
Marburg virus–associated uveitis, intraocular pressure
was markedly elevated (9,21). Although Ebola-related
acute uveitis has been reported to be associated with high
intraocular pressure, we did not find any evidence of per-
sistently high intraocular pressure in survivors with Ebola
retinal lesions.
Uveitis accounts for 24% of blindness in Sierra Leone
and is second only to cataracts as the leading cause (23).
A proportion of those cataracts might be a consequence of
intraocular inflammation, especially in younger patients.
Given the high endemic rates of parasitic, viral, and fungal

1106 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 23, No. 7, July 2017
 Retinal Lesion in Ebola Survivors, Sierra Leone

Figure 3. Characteristic
features of lesions observed
in a case–control study of
ocular signs in Ebola virus
disease survivors, Sierra
Leone, 2016. A) Composite
scanning laser ophthalmoscope
retinal image, left eye. Arrow
indicates direction of the optical
coherence tomography scan.
B) Optical coherence
tomography. White, long,
dashed line indicates cross-
sectional plane; white
arrowhead indicates Ebola
lesion limited to the retinal
layers with an intact retinal
pigment epithelium.
C) Examples of straight-
edged, sharp angulated lesions
(magnified from panel A 1.5×).
D) Example of tangential section through the human fovea with illustrative highlighting of a triangular photoreceptor matrix
corresponding to Ebola lesional shape. Courtesy of Ahnelt et al. (17).

disease in the region, infectious uveitis is likely to have a
higher prevalence than in Western populations (24). Nev-
ertheless, the proportion of controls with chorioretinal le-
sions and retinal vasculitis was surprising. Pigmented and
atrophic chorioretinal scars not in keeping with the Ebola
retinal lesions were no more common in EVD survivors
than controls, and it is important not to attribute these find-
ings to EBOV infection in survivors documented in case
series (7,12).
The leading cause of uveitis in Sierra Leone is oncho-
cerciasis, but this disease is in decline because of the sys-
tematic distribution of ivermectin to affected areas (25,26).
The rate of other uveitis-associated blindness appears to be
increasing in Sierra Leone (23). This study was conduct-
ed in Freetown, where the incidence of onchocerciasis is
lower than in rural regions, and other causes are probably
responsible. Toxoplasmosis accounted for 43% of symp-
tomatic cases of posterior uveitis in 1 study (27), and it
was probably a common cause among the patients in our
study, although no serologic testing for toxoplasmosis was
available. HIV prevalence in persons >15 years of age in
Sierra Leone was estimated to be 1.25% in 2015 (28). The
Ebola outbreak disrupted the fragile health system, includ-
ing HIV reporting mechanisms and AIDS response (29).
This HIV rate is still relatively low compared with many
other African nations. Further diagnostic investigation is
required to attempt to attribute causation to the various cho-
rioretinal lesions observed in this study. Geographic areas
of retinal whitening (white without pressure) are thought
to be normal variants (30,31). Areas of retinal darkening
(dark without pressure) have previously been attributed to
sickle cell disease (32).
Our study is subject to 1 limitation with regard to the
control group, who were selected opportunistically with un-
matched cases and controls, and differences in age and sex
ratios between the groups. This fact reflects the difficulties
and limitations of conducting research in the post-Ebola set-
ting in Freetown in 2016. The study was conducted in a mili-
tary hospital, which housed the Ebola treatment unit and the
continuing EVD survivors clinic. The hospital also serves
the local civilian community and a military barracks com-
munity. The use of a non-EVD control group, even with-
out matching, allowed a comparison in the fundus findings
between post-EVD and control groups. We found a higher
prevalence of retinal disease in the symptomatic clinic-at-
tending control group than in the asymptomatic population
control group; both groups included some military mem-
bers of staff and families. This comparison allows us to be
more positive about the specificity of the Ebola retinal le-
sion. Given our aim to compare EVD with non-EVD fundus
findings, an age- and sex-matched population control group
probably would not change the study conclusions.
EVD survivors were identified by the possession of
an Ebola treatment center discharge certificate. Forgery of
these certificates has been known given the free access to
healthcare it confers. IgG confirmation of previous EBOV
infection is planned for ongoing follow-up studies. Our
study provides information on the medium-term ocular se-
quelae of EVD survivors with a median time of 411 days
since hospital discharge. Our study does not provide data
on acute uveitis and ocular disease in the immediate after-
math of EVD as reported elsewhere (2,4,6).
Although we can reasonably conclude the retinal
lesions described in our study are sequelae of EVD, no

Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 23, No. 7, July 2017 1107
RESEARCH
pre-EVD retinal imaging was available to conclusive-
ly identify the timing of acquisition of the lesions. Our
control group demonstrates the common retinal signs
and pathologies that are present in the population before
Ebola exposure.
We have documented a novel retinal abnormality in
EVD survivors that appears to be specific to EVD, al-
though the proportion in the cohort with the condition is
small. The background prevalence of chorioretinal ab-
normalities, including scarring with pigmentation, in the
population is high and should not be attributed to EVD.
Although further studies with larger sample sizes are re-
quired, EBOV does not necessarily persist in the aqueous
humor of those with cataracts and no ongoing intraocular
inflammation. These initial results raise the possibility of
safe cataract surgery for EVD survivors with no signs of
ongoing intraocular inflammation.
Acknowledgments
We thank Wallace L.M. Alward for permission to use his
retinal nerve fiber layer illustration; Optos PLC for their
generous donation of the Daytona Ophthalmoscope, which
continues to improve patient care for the people of Sierra
Leone; Onlime SL Ltd. for supplying the clinics at 34th
Regiment Military Hospital with internet access; Medisoft, for
the offer of electronic patient record software (although not
used in this study); and the administration at 34th Regiment
Military Hospital for supporting and facilitating the study and
for upgrading the eye clinic. Thank you to the patients and
subjects for agreeing to participate in this study.
This work was funded by The Dowager Countess Eleanor Peel
Trust, Bayer Global Ophthalmology Awards Programme, and
Enhancing Research Activity in Epidemic Situations (ERAES)
Wellcome Trust Programme. The sponsors of the study had
no role in study design, data collection, data analysis, data
interpretation, or writing of the manuscript. In addition, J.T.S.
and M.G.S. are supported by the National Institute for Health
Research Health Protection Research Unit in Emerging and
Zoonotic Infections at the University of Liverpool.
P.J.S. had full access to all the data in the study and takes
responsibility for the integrity of the data and the accuracy of the
data analysis. P.J.S., J.T.S., N.A.V.B., and M.G.S. conceived and
designed the study. P.J.S., J.T.S., and M.G.S. wrote the ethics
submission. P.J.S., J.T.S., and M.G.S. wrote the specimen
collection protocols. P.J.S., J.T.S., and M.G.S. wrote the consent
forms, and F.M., A.D.F., and P.K. translated them into Krio.
P.J.S. trained and initially supervised staff in ophthalmic
examination and imaging. M.G.S. supervised consent and
aqueous humor specimen collection/transport and maintained
quality assurance over procedures. P.J.S. and F.M. undertook
aqueous humor collection. P.J.S., F.M., A.D.F., and P.K. were
responsible for data collection and data storage. P.J.S., M.G.S.,
1108 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 23, No. 7, July 2017
and N.A.V.B. developed the classification of image
abnormalities and the data analysis plan. P.J.S., C.K.P., R.D.,
J.M.B., and N.A.V.B. performed image grading and the data
analysis. N.A.V.B. provided the final arbitration of image
grading. P.J.S., J.T.S., and G.C. wrote the statistical analysis
plan. J.R. performed aqueous humor laboratory analysis. P.J.S.
and N.A.V.B. drafted the manuscript. P.J.S. and M.G.S. drafted
the paper, and all other authors reviewed and approved the
final version.
Dr. Steptoe is a clinical research fellow at the University
of Liverpool and a specialist ophthalmology trainee in the
Mersey region, UK. His research interests include tropical
ophthalmology with an emphasis on ophthalmic infections
and uveitis.
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Address for correspondence: Paul J. Steptoe, Institute in the Park, Alder
Hey Children’s Hospital, Eaton Rd, Liverpool, Merseyside, L12 2AP,
UK; email: paul.steptoe@liverpool.ac.uk

EID SPOTLIGHT TOPIC

Ebola, previously known as Ebola hemorrhagic fever, is a rare and deadly disease
caused by infection with one of the Ebola virus strains. Ebola can cause disease in
humans and nonhuman primates (monkeys, gorillas, and chimpanzees).
Ebola is caused by infection with a virus of the family Filoviridae, genus Ebolavirus.
There are five identified Ebola virus species, four of which are known to cause
disease in humans. Ebola viruses are found in several African countries; they
were first discovered in 1976 near the Ebola River in what is now the Democratic
Republic of the Congo. Before the current outbreak, Ebola had appeared

Ebola
sporadically in Africa.
The natural reservoir host of Ebola virus remains unknown. However, on the basis
of evidence and the nature of similar viruses, researchers believe that the virus
is animal-borne and that bats are the most likely reservoir. Four of the five virus
strains occur in an animal host native to Africa.

®
http://wwwnc.cdc.gov/eid/page/ebola-spotlight

Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 23, No. 7, July 2017 1109